I am sorry to have been so long in responding to your questions but I was away from the lab for the first several weeks of
November. You have raised interesting and serious questions, and the response to each would, if complete, be quite lengthy.
Therefore, I will only comment briefly on your points. I will try to discuss a few matters which I believe to be important
in trying to work out answers, rather than giving you any answers.

A. To knowledge there has been no rigorous description of the often mentioned possible impact of recombinant DNA experiments
on evolution. For example . . . it is not clear what species are of concern. Is it the evolution of the bacterial or viral
host-vector system, or the evolution of complex organisms that is of concern? For each type of organism, different questions
arise. Furthermore, there is at present substantial scholarly dispute about mechanisms of evolution for higher organisms,
thus confounding the difficulty of analyzing the possible effect of recombinant DNA experiments. Those who have raised the
evolutionary argument as a reason for avoiding recombinant DNA experiments have never, to my knowledge, analyzed these sorts
of questions.

B. I myself am not competent to discuss gene pools and their evolution. The relative advantages and disadvantages of treating
genetic diseases by somatic or genetic approaches has seemed to ne a very difficult question. It may well be that we simply
have insufficient evidence to deal with this question at present.

C. Yes, I do think that there is now hard evidence that indicates that shotgun experiments using E. coli host-vector system
are not likely to be hazardous. Recall that the initial discussion never said that they would be hazardous, but only that
we didn't know and should therefore take an extremely conservative approach. However it is now clear, as documented in
the report of the Falmouth meeting of June 1977 and published in the Journal of Infectious Diseases, that the present E. coli
host-vector have an extremely low probability of survival outside of the laboratory thus diminishing greatly any concern about
shotgun experiments is such systems.

D. I suspect that voluntary control of industrial work in the recombinant DNA field will probably not be sufficient. However,
new federal legislation is not the only answer to this problem. There are many individuals who believe that existing authorities,
in the FDA, OSHA, and Department of Commerce may provide the framework for meaningful, non-voluntary control of the private
sector.

E. There is accumulating evidence indicating that B. subtilis, and especially the non-spore-forming mutants, provide safe
and effective host-vector systems for some recombinant DNA work.

F. I agree with Dr. Zinder's characterization so long as it is restricted to some critics. I do not believe that all the
critics fall into this class.